Inactivated recombinant influenza vaccine: the promising direction for the next generation of influenza vaccine

ABSTRACT

Introduction

Vaccination is the most effective method to control the prevalence of seasonal influenza and the most widely used influenza vaccine is the inactivated influenza vaccine (IIV). Each season, the influenza vaccine must be updated to be most effective against current circulating variants. Therefore, developing a universal influenza vaccine (UIV) that can elicit both broad and durable protection is of the utmost importance.

Area covered

This review summarizes and compares the available influenza vaccines in the market and inactivation methods used for manufacturing IIVs. Then, we discuss the latest progress of the UIV development in the IIV format and the challenges to address for moving these vaccine candidates to clinical trials and commercialization. The literature search was based on the Centers for Disease Control and Prevention (CDC) and the PubMed databases.

Expert opinion

The unmet need for UIV is the primary aim of developing the next generation of influenza vaccines. The IIV has high antigenicity and a refined manufacturing process compared to most other formats. Developing the UIV in IIV format is a promising direction with advanced biomolecular technologies and next-generation adjuvant. It also inspires the development of universal vaccines for other infectious diseases.

KEYWORDS:

• Beta-propiolactone
• formaldehyde
• inactivated influenza vaccine
• hemagglutinin
• universal influenza vaccine
• reverse transgenic rescued influenza virus
• adjuvant

Article highlights

• There are inactivated influenza vaccine (IIV), live attenuated influenza vaccine (LAIV), and recombinant influenza vaccine (RIV) available in the U.S. market, but IIV has the longest history of human use.

• Beta-propiolactone (BPL) inactivates multiple influenza subtypes more completely and retains antigenicity better than formaldehyde (FA).

• Reverse transgenic technology is used to enhance the yield of IIV by reassorting the selected strain with high-speed growth strain.

• Various strategies are developed to elicit cross-protection against multiple drifted strains. Designing the inactivated recombinant influenza virus carrying modified antigens provides a promising direction for developing a UIV with a simple manufacturing process.

Declaration of interests

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

HS and TMR conceptualized and designed this work. HS drafted this manuscript. TMR reviewed and revised this manuscript. All authors contributed to, revised, and improved the final manuscript.

Acknowledgments

TM Ross is also supported in part as an Eminent Scholar by the Georgia Research Alliance, GRA-001. Benjamin Chadwick helped proofread this work for language editing.

Additional information

Funding

This manuscript was funded by the National Institute of Allergy and Infectious Diseases, a component of the NIH, Department of Health and Human Services, under the Collaborative Influenza Vaccine Innovation Center (CIVIC) Contract [75N93019C00052].